Project Summary: The long range objective of my research is to understand how the retina conveys visual information to the brain in the ensemble activity of many retinal ganglion cells, and how this signaling influences visual perception and behavior, in health and in disease. A major unsolved problem is how the numerically dominant cell types in the primate retina - midget, parasol and small bistratified cells - are spatially organized to represent the visual scene. Specifically, there are major gaps in our understanding of the mosaic coverage of visual space by their receptive fields (RFs), the fine structure and local organization of RFs, and the homogeneity of response properties within each cell type. We have recently completed collaborative development of a unique 512-electrode recording system capable of surveying the response properties of several hundred parasol, midget and small bistratified RGCs simultaneously in a 1x2 mm region of retina, allowing us to probe the mosaic RF organization of these major cell types for the first time. We have also developed techniques to probe the structure of RFs at the elementary resolution of the retina: single cones. We will use this unique combination of approaches to: (1) test whether midget and parasol cell RFs sample the visual scene with equal and independent coverage;(2) test whether individual RFs exhibit interdigitated fine structure that produces more uniform coverage of the visual field;and (3) test whether each cell type is irreducible or whether physiological subtypes are interleaved in each mosaic. Relevance: The midget, parasol and small bistratified cells constitute ~80%of ganglion cells in the primate retina and convey by far the highest acuity representation of the visual scene to the brain. Their functional organization is crucial for healthy visual function. Retinas with degraded RF mosaics, or displaying unusually variable light responses within a mosaic, would be expected to produce degraded visual function. Therefore, understanding the normal functional organization will be useful in diagnosis of visual disease. Furthermore, prosthetic devices to replace retinal function, which are now being tested in humans, will eventually need to reproduce the normal regularity and coordination between cell types in order to provide natural visual signals to the brain. Our recent experiments using electrical stimulation with multi-electrode arrays for prosthetic design will benefit greatly from understanding the functional organization of the major RGC types in primate retina. In summary, knowing the functional organization of parasol, midget and small bistratified cells is a key element in understanding the healthy visual system and designing prosthetic treatments for retinas damaged by disease.